TBX2

T-box transcription factor 2, the group of T-box transcription factors

Basic information

Region (hg38): 17:61399842-61409466

Links

ENSG00000121068 ∙ NCBI:6909 ∙ OMIM:600747 ∙ HGNC:11597 ∙ Uniprot:Q13207 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• vertebral anomalies and variable endocrine and T-cell dysfunction (Limited), mode of inheritance: AD
• vertebral anomalies and variable endocrine and T-cell dysfunction (Limited), mode of inheritance: AD
• vertebral anomalies and variable endocrine and T-cell dysfunction (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Vertebral anomalies and variable endocrine and T-cell dysfunction	AD	Allergy/Immunology/Infectious; Endocrine	The condition can include endocrine dysfunction, and awareness may allow prompt diagnosis and management; Immune deficiency has been described, and awareness may allow preventative measures and prompt treatment of infections	Allergy/Immunology/Infectious; Cardiovascular; Craniofacial; Endocrine; Musculoskeletal; Neurologic	29726930

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TBX2 gene.

• Inborn genetic diseases (29 variants)
• not provided (28 variants)
• Vertebral anomalies and variable endocrine and T-cell dysfunction (14 variants)
• TBX2-related condition (4 variants)
• not specified (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TBX2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				16	6	22
missense		2	37	1	3	43
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding					5	5
Total	0	2	38	17	14

Variants in TBX2

This is a list of pathogenic ClinVar variants found in the TBX2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-61400185-G-A			Likely benign (Oct 05, 2017)
17-61400197-G-C		TBX2-related disorder	Likely benign (Aug 01, 2023)
17-61400235-G-A		TBX2-related disorder • Vertebral anomalies and variable endocrine and T-cell dysfunction	Pathogenic/Likely pathogenic (Sep 05, 2022)
17-61400286-T-G		Vertebral anomalies and variable endocrine and T-cell dysfunction	Likely pathogenic (Jul 07, 2020)
17-61400307-C-A		not specified	Uncertain significance (Nov 21, 2022)
17-61400328-C-A		not specified	Uncertain significance (Jun 06, 2023)
17-61400340-C-T		not specified	Uncertain significance (Jan 16, 2024)
17-61400343-G-A		not specified	Uncertain significance (Oct 05, 2023)
17-61400352-G-A		not specified	Uncertain significance (May 24, 2023)
17-61400362-C-CGCG		TBX2-related disorder	Likely benign (Oct 31, 2023)
17-61400367-C-T		not specified	Uncertain significance (May 05, 2023)
17-61400377-G-T		TBX2-related disorder	Likely benign (Apr 19, 2023)
17-61400404-C-A		TBX2-related disorder	Likely benign (Sep 22, 2023)
17-61400416-G-A		TBX2-related disorder	Likely benign (Feb 15, 2021)
17-61400445-G-T		not specified	Uncertain significance (Feb 06, 2024)
17-61400500-G-C			Likely benign (Sep 21, 2017)
17-61400522-G-A		not specified	Uncertain significance (Dec 27, 2022)
17-61400542-C-A		TBX2-related disorder	Benign (Aug 13, 2019)
17-61400567-G-C		not specified	Uncertain significance (Oct 04, 2022)
17-61401712-G-C		not specified	Uncertain significance (Feb 10, 2022)
17-61401719-G-T		Vertebral anomalies and variable endocrine and T-cell dysfunction	Uncertain significance (May 14, 2023)
17-61401765-C-T			Likely benign (Jan 12, 2018)
17-61401769-G-A		Vertebral anomalies and variable endocrine and T-cell dysfunction	Uncertain significance (Sep 27, 2022)
17-61401787-T-C		Vertebral anomalies and variable endocrine and T-cell dysfunction	Likely pathogenic (-)
17-61401842-G-A		not specified	Uncertain significance (Nov 15, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TBX2	protein_coding	protein_coding	ENST00000240328	7	9571

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.993	0.00671	119725	0	1	119726	0.00000418

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.54	288	371	0.775	0.0000206	4454
Missense in Polyphen		130	177.36	0.73297		2021
Synonymous	1.11	151	169	0.892	0.0000103	1535
Loss of Function	3.86	1	19.3	0.0518	0.00000104	229

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000557	0.0000557
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.0000557	0.0000557
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the transcriptional regulation of genes required for mesoderm differentiation. Probably plays a role in limb pattern formation. Acts as a negative regulator of PML function in cellular senescence. May be required for cardiac atrioventricular canal formation. {ECO:0000269|PubMed:22002537}.
• Pathway: Heart Development;Kit receptor signaling pathway;tumor suppressor arf inhibits ribosomal biogenesis (Consensus)

Recessive Scores

• pRec: 0.228

Haploinsufficiency Scores

• pHI: 0.955
• hipred: Y
• hipred_score: 0.875
• ghis: 0.594

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.994

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Tbx2
• Phenotype: embryo phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); digestive/alimentary phenotype; limbs/digits/tail phenotype; growth/size/body region phenotype; craniofacial phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: tbx2a
• Affected structure: pronephric distal late tubule
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;heart looping;outflow tract septum morphogenesis;outflow tract morphogenesis;endocardial cushion morphogenesis;regulation of transcription from RNA polymerase II promoter involved in myocardial precursor cell differentiation;Notch signaling pathway;muscle cell fate determination;cell aging;regulation of heart contraction;positive regulation of cell population proliferation;embryonic heart tube development;aorta morphogenesis;atrioventricular canal development;embryonic digit morphogenesis;negative regulation of transcription, DNA-templated;embryonic camera-type eye morphogenesis;cardiac muscle tissue development;roof of mouth development;positive regulation of cardiac muscle cell proliferation;pharynx development;developmental growth involved in morphogenesis;mammary placode formation;cellular senescence;negative regulation of heart looping;negative regulation of cardiac chamber formation
• Cellular component: nucleus;transcription factor complex
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA binding;protein binding;sequence-specific DNA binding